期刊论文详细信息
Investigation of vascular responses in endothelial nitric oxide synthase/cyclooxygenase-1 double-knockout mice - Key role for endothelium-derived hyperpolarizing factor in the regulation of blood pressure in vivo
Article
关键词: ESTROGEN-RECEPTOR-BETA;    MESENTERIC-ARTERIES;    NATRIURETIC PEPTIDE;    GAP-JUNCTIONS;    RESISTANCE VESSELS;    CEREBRAL-ARTERIES;    CORONARY-ARTERIES;    GENE DISRUPTION;    CAROTID-ARTERY;    MOUSE AORTA;   
DOI  :  10.1161/01.CIR.0000155238.70797.4E
来源: SCIE
【 摘 要 】

Background - Endothelium-dependent dilatation is mediated by 3 principal vasodilators: nitric oxide (NO), prostacyclin (PGI(2)), and endothelium-derived hyperpolarizing factor (EDHF). To determine the relative contribution of these factors in endothelium- dependent relaxation, we have generated mice in which the enzymes required for endothelial NO and PGI(2) production, endothelial NO synthase (eNOS) and cyclooxygenase-1 (COX-1), respectively, have been disrupted (eNOS(-/-) and COX-1(-/-) mice). Methods and Results - In female mice, the absence of eNOS and COX-1 had no effect on mean arterial blood pressure (BP), whereas BP was significantly elevated in eNOS(-/-)/ COX-1(-/-) males compared with wild-type controls. Additionally, endothelium- dependent relaxation remained intact in the resistance vessels of female mice and was associated with vascular smooth muscle hyperpolarization; however, these responses were profoundly suppressed in arteries of male eNOS(-/-)/ COX-1(-/-) animals. Similarly, the endothelium- dependent vasodilator bradykinin produced dose-dependent hypotension in female eNOS(-/-)/ COX-1(-/-) animals in vivo but had no effect on BP in male mice. Conclusions - These studies indicate that EDHF is the predominant endothelium- derived relaxing factor in female mice, whereas NO and PGI(2) are the predominant mediators in male mice. Moreover, the gender-specific prevalence of EDHF appears to underlie the protection of female eNOS(-/-)/ COX-1(-/-) mice against hypertension.

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